Queensland Micro- and Nanotechnology Centre, Griffith University, Brisbane 4111, Australia; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane 4072, Australia.
Centre of Advanced Imaging, University of Queensland, Brisbane 4072, Australia.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112477. doi: 10.1016/j.msec.2021.112477. Epub 2021 Oct 18.
In this study, modular two-in-one nano-cocktails were synthesised to provide treatment of inflammatory diseases and also enable tracking of their delivery to the disease sites. Chitosan nano-cocktails loaded with treatment module (cerium oxide nanoparticles) and imaging module (iron oxide nanoparticles) were synthesised by electrostatic self-assembly (Chit-IOCO) and ionic gelation method (Chit-TPP-IOCO), respectively. Their MRI capability, anti-inflammatory and anti-fibrosis ability were investigated. Results demonstrated that Chit-IOCO significantly reduced the expression of TNF-α and COX-2, while Chit-TPP-IOCO reduced IL-6 in the LPS-stimulated macrophages RAW264.7. Cytotoxicity studies showed that the nano-cocktails inhibited the proliferation of macrophages. Additionally, Chit-IOCO exhibited higher in vitro MRI relaxivity than Chit-TPP-IOCO, indicating that Chit-IOCO is a better MRI contrast agent in macrophages. It was possible to track the delivery of Chit-IOCO to the inflamed livers of CCl-treated C57BL/6 mice, demonstrated by a shortened T relaxation time of the livers after injecting Chit-IOCO into mice. In vivo anti-inflammatory and blood tests demonstrated that Chit-IOCO reduced inflammation-related proteins (TNF-a, iNOS and Cox-2) and bilirubin in CCl treated C57BL/6. Histology images indicated that the nano-cocktails at the treatment doses did not affect the organs of the mice. Importantly, the nano-cocktail reduced fibrosis of CCl-treated mouse liver. This is the first reported data on the anti-inflammation and anti-fibrosis efficacy of Chit-IOCO in C57BL/6 mouse liver inflammation model. Overall, Chit-IOCO nanoparticles have shown great potential in MR imaging/detecting and treating/therapeutic capabilities for inflammatory diseases.
在这项研究中,合成了模块化的二合一纳米鸡尾酒,以提供治疗炎症性疾病的方法,并能够跟踪其递送至疾病部位。通过静电自组装(壳聚糖-IOCO)和离子凝胶化方法(壳聚糖-TPP-IOCO)分别合成了负载治疗模块(氧化铈纳米颗粒)和成像模块(氧化铁纳米颗粒)的壳聚糖纳米鸡尾酒。研究了它们的 MRI 能力、抗炎和抗纤维化能力。结果表明,壳聚糖-IOCO 显著降低了 LPS 刺激的 RAW264.7 巨噬细胞中 TNF-α 和 COX-2 的表达,而壳聚糖-TPP-IOCO 降低了 IL-6 的表达。细胞毒性研究表明,纳米鸡尾酒抑制了巨噬细胞的增殖。此外,壳聚糖-IOCO 的体外 MRI 弛豫率高于壳聚糖-TPP-IOCO,表明壳聚糖-IOCO 是巨噬细胞中更好的 MRI 对比剂。通过向 CCl 处理的 C57BL/6 小鼠注射 Chit-IOCO 后,肝脏 T 弛豫时间缩短,可以追踪 Chit-IOCO 递送至炎症肝脏。体内抗炎和血液测试表明,壳聚糖-IOCO 降低了 CCl 处理的 C57BL/6 中的炎症相关蛋白(TNF-a、iNOS 和 Cox-2)和胆红素。组织学图像表明,纳米鸡尾酒在治疗剂量下不影响小鼠的器官。重要的是,纳米鸡尾酒减少了 CCl 处理的小鼠肝脏纤维化。这是首次报道壳聚糖-IOCO 在 C57BL/6 小鼠肝脏炎症模型中具有抗炎和抗纤维化作用的数据。总之,壳聚糖-IOCO 纳米颗粒在炎症性疾病的 MRI 成像/检测以及治疗/治疗能力方面显示出巨大的潜力。
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